Skin repairing potential of ellagic acid-loaded zein nanoparticles: Chemical and biopharmaceutical characterization, enzymatic inhibition and cytotoxicity over keratinocytes

Zein has demonstrated the ability to carry different therapeutic molecules in the form of nano delivery systems. Ellagic acid (EA) has improved its biological properties when associated with zein. In this study, we aimed to evaluate the biopharmaceutical and in vitro pharmacological potential on skin maintenance and repairing processes, sun protection and cytotoxicity. The nanoparticles were produced by nanoprecipitation and characterized in terms of morphology, size, polydispersity, zeta potential, encapsulation efficiency, drug loading and release efficiency. The effect of ellagic acid loaded-zein nanoparticles over enzymes related to the skin protective and repairing processes was accessed. Anti-hyaluronidase, anti-lipoxygenase, anti-elastase, anti-collagenase, antityrosinase and photoprotective activities were determined spectrophotometrically, while the hemolytic activity was evaluated using erythrocytes and MTT and NRU assays were used to evaluate the cytotoxicity over immortalized human keratinocytes (HaCaT) and squamous carcinoma cells (A431). The chemical interactions between EA and zein were studied by steady-state fluorescence spectroscopy. EA-loaded zein nanoparticles (NE) were spherical, homogeneous and monodisperse, with a size of 370 nm, encapsulation efficiency over 82%. The nanoparticles demonstrated a sustained release profile under different pH. Regarding the anti-enzymatic activities, NE presented an inhibitory potency over 38% for all enzymes tested. NE did not present hemolytic activity and showed limited cytotoxicity over HaCaT cells. Moreover, NE also presented an SPF of 29.88. The interaction between zein and EA was driven by a dynamic quenching mechanism. Therefore, NE present a great potential to aid in skin protection/repairing processes, such as wound treatments.

Automated summary

In this study, zein nanoparticles loaded with ellagic acid (EA) were prepared using a nanoprecipitation method. The nanoparticles were spherical, homogeneous, and monodisperse with a size of 370 nm and encapsulation efficiency of over 82%. The results demonstrated that the EA-loaded zein nanoparticles exhibited excellent skin protection and repairing abilities, inhibitory effects on multiple skin enzymes, no hemolytic activity, limited cytotoxicity on HaCaT cells, and an SPF value of 29.88. Therefore, the nanoparticles show great potential in skin protection and repairing processes.